For many, Alzheimer's disease is the number one medical issue facing our aging society. It is typically thought to be a late onset neurodegenerative disease that impairs memory and cognitive performance. Symptoms frequently include decreased functional capacity and negative psychological attributes (e.g., depression, anxiety) in association with the memory and cognition deficits.
The prevalence of dementia in North America is approximately 6 to 10% of the population, with Alzheimer's disease accounting for a substantial portion of these cases. This illness represents a steadily growing medical and social problem of our aging societies around the World. Some believe the main pathological features may relate to intraneuronal neurofibrillary tangles, formation of amyloid beta plaques and/or neurodegeneration of mainly cholinergic and, in later stages, also serotonergic, noradrenergic, and other neurons, resulting in deficiencies of acetylcholine and other neurotransmitters. Some theories suggest that the gradual development of an acetylcholine signaling deficiency may be responsible for the early clinical manifestations of Alzheimer's disease. Consequently, some believe that compounds that improve cholinergic functioning, such as acetylcholine esterase inhibitors may ameliorate the cognitive deficits in patients with Alzheimer's disease. The most widely used acetylcholine esterase inhibitor is donepezil hydrochloride (Aricept®).
Acetylcholine esterase inhibitor medications are designed to increase acetylcholine levels, a neurotransmitter that is severely reduced in the brain of patients with Alzheimer's disease. Rogers reports that treatment with an acetylcholine esterase inhibitor typically results in an increase of approximately 2.5-3.1 points on the cognitive subscale of the Alzheimer's disease assessment scale (ADAS-Cog) from baseline over placebo (Rogers, 1998). Cummings reports that improvements in cognition modestly exceed the threshold considered to be clinically relevant and typically last for 6 months (Cummings, 2001). Therefore, more efficacious drugs are urgently needed to provide treatment for cognitive impairments such as for patients with Alzheimer's disease.